
Use of PEGylated Immunoliposomes to Deliver Dopamine Across the Blood–Brain Barrier in a Rat Model of Parkinson's Disease
Author(s) -
Kang YoungSook,
Jung HyunJoo,
Oh JiSuk,
Song DaeYong
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12580
Subject(s) - blood–brain barrier , liposome , pharmacology , dopamine , chemistry , drug delivery to the brain , medicine , biochemistry , central nervous system
Summary Aim To treat neurodegenerative disorders such as Parkinson's disease ( PD ), drugs must be able to cross the blood–brain barrier ( BBB ). Patients with PD are deficient in dopamine ( DA ), a neurotransmitter that cannot pass through the BBB . Liposomes modified by adding polyethylene glycol ( PEG ylated liposomes ( PL s)) can be conjugated with antibody to form DA – PEG ylated immunoliposomes ( DA ‐ PIL s), and we tested their use as carriers of DA for treating PD . Methods PEG ylated liposomes ( PL s) were prepared by evaporation method, and [ 3 H]dopamine was encapsulated within the dried lipid film using a freeze/thaw cycle to form DA ‐ PL . Thiolated OX 26 MA b, an antitransferrin receptor monoclonal antibody, was then conjugated to 46‐nm PEG ylated liposomes. Particle size, zeta potential, and stability were assessed, and in vivo effects were determined after the intravenous injection of DA , DA ‐ PL , and DA ‐ PIL by examining brain tissue in normal rats and rats that underwent transection of the medial forebrain bundle to induce PD . Results The uptake of DA ‐ PIL in the brains of this PD rat model increased about 8‐fold compared with that of DA alone and about 3‐fold compared with that of encapsulated DA – PEG ylated liposomes ( DA ‐ PL ). The volume of distribution of DA ‐ PIL in the brain by the perfusion method was 4‐fold higher than that of DA ‐ PL , indicating that conjugation of OX 26 MA b to the transferrin receptor of brain capillary endothelium mediated the effective delivery of DA to brain tissue. Conclusions Dopamine can be effectively delivered to the brain by means of a PIL ‐based drug delivery system in PD rats.